Whole-exome sequencing identifies MST1R as a genetic susceptibility gene in nasopharyngeal carcinoma.

Multiple factors, including host genetics, environmental factors, and Epstein-Barr virus (EBV) infection, contribute to nasopharyngeal carcinoma (NPC) development. To identify genetic susceptibility genes for NPC, a whole-exome sequencing (WES) study was performed in 161 NPC cases and 895 controls of Southern Chinese descent. The gene-based burden test discovered an association between macrophage-stimulating 1 receptor (MST1R) and NPC. We identified 13 independent cases carrying the MST1R pathogenic heterozygous germ-line variants, and 53.8% of these cases were diagnosed with NPC aged at or even younger than 20 y, indicating that MST1R germline variants are relevant to disease early-age onset (EAO) (age of ≤20 y). In total, five MST1R missense variants were found in EAO cases but were rare in controls (EAO vs. control, 17.9% vs. 1.2%, P = 7.94 × 10(-12)). The validation study, including 2,160 cases and 2,433 controls, showed that the MST1R variant c.G917A:p.R306H is highly associated with NPC (odds ratio of 9.0). MST1R is predominantly expressed in the tissue-resident macrophages and is critical for innate immunity that protects organs from tissue damage and inflammation. Importantly, MST1R expression is detected in the ciliated epithelial cells in normal nasopharyngeal mucosa and plays a role in the cilia motility important for host defense. Although no somatic mutation of MST1R was identified in the sporadic NPC tumors, copy number alterations and promoter hypermethylation at MST1R were often observed. Our findings provide new insights into the pathogenesis of NPC by highlighting the involvement of the MST1R-mediated signaling pathways.

Asian expert recommendation on management of skin and mucosal effects of radiation, with or without the addition of cetuximab or chemotherapy, in treatment of head and neck squamous cell carcinoma.

With increasing numbers of patients with unresectable locoregionally advanced (LA) head and neck squamous cell carcinoma (HNSCC) receiving cetuximab/radiotherapy (RT), several guidelines on the early detection and management of skin-related toxicities have been developed. Considering the existing management guidelines for these treatment-induced conditions, clinical applicability and standardization of grading methods has remained a cause of concern globally, particularly in Asian countries. In this study, we attempted to collate the literature and clinical experience across Asian countries to compile a practical and implementable set of recommendations for Asian oncologists to manage skin- and mucosa-related toxicities arising from different types of radiation, with or without the addition of cetuximab or chemotherapy. In December 2013, an international panel of experts in the field of head and neck cancer management assembled for an Asia-Pacific head and neck cancer expert panel meeting in China. The compilation of discussion outcomes of this meeting and literature data ultimately led to the development of a set of recommendations for physicians with regards to the approach and management of dermatological conditions arising from RT, chemotherapy/RT and cetuximab/RT, and similarly for the approach and management of mucositis resulting from RT, with or without the addition of chemotherapy or cetuximab. These recommendations helped to adapt guidelines published in the literature or text books into bedside practice, and may also serve as a starting point for developing individual institutional side-effect management protocols with adequate training and education.

Autologous hematopoietic stem cell transplantation in extranodal natural killer/T cell lymphoma: a multinational, multicenter, matched controlled study.

Extranodal natural killer (NK)/T cell lymphoma, nasal type, is a recently recognized distinct entity and the most common type of non-B cell extranodal lymphoma in Asia. This retrospective analysis studied the potential survival benefits of hematopoeitic stem cell transplantation (HSCT) compared with a historical control group. A total of 47 patients from 3 previously published series of HSCT were matched according to NK/T cell lymphoma International Prognostic Index (NKIPI) risk groups and disease status at transplantation with 107 patients from a historical control group for analysis. After a median follow-up of 116.5 months, the median survival time was not determined for the HSCT group, but it was 43.5 months for the control group (95% confidence interval [CI] = 6.7 to 80.3 months; P = .127, log-rank test). In patients who were in complete remission (CR) at the time of HSCT or at surveillance after remission, disease-specific survival rates were significantly higher in the HSCT group compared with the control group (disease-specific 5-year survival rate, 87.3% for HSCT vs 67.8% for non-HSCT; P = .027). In contrast, in subgroup analysis on non-CR patients at the time of HSCT or non-HSCT treatment, disease-specific survival rates were not significantly prolonged in the HSCT group compared with the control group (1-year survival rate, 66.7% for HSCT vs 28.6% for non-HSCT; P = .141). The impact of HSCT on the survival of all patients was significantly retained at the multivariate level with a 2.1-fold (95% CI =1.2- to 3.7-fold) reduced risk of death (P = .006). HSCT seems to confer a survival benefit in patients who attained CR on postremission consolidation therapy. These findings suggest that, in particular, patients in CR with high NKIPI risk scores at diagnosis should receive full consideration for HSCT.

Hong Kong Consensus Statements for the Management of Unresectable Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is highly prevalent in Hong Kong due to the high prevalence of chronic hepatitis B infection. Liver cancer is the fourth most common cancer and the third most common cause of cancer death. Due to the high case load, there is a high level of local expertise in treating HCC, and the full spectrum of treatment modalities is available. This document summarizes how these modalities should be used based on the latest evidence. SUMMARY: In 2 meetings held in early 2017, a multidisciplinary group of Hong Kong clinicians, including liver surgeons, interventional radiologists, clinical oncologists, and medical oncologists, met to update local consensus statements for management of HCC. These statements are based on the latest evidence and give detailed guidance on how to deploy these modalities, in particular for cases of HCC which are not suited to surgical resection. KEY MESSAGES: These statements give detailed information on how to decide if a patient is a candidate for resection, methods to improve candidacy for resection, and guidance for use of various nonsurgical interventions to manage patients ineligible for resection.

Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy.

BACKGROUND & AIMS: Hepatitis B virus reactivation is a serious cause of morbidity and mortality in hepatitis B surface antigen-positive patients treated with chemotherapy. We compared the efficacy of early and deferred preemptive lamivudine therapy in reducing the incidence of hepatitis due to hepatitis B virus reactivation in hepatitis B surface antigen-positive lymphoma patients treated with chemotherapy. METHODS: Thirty consecutive hepatitis B surface antigen-positive lymphoma patients undergoing intensive chemotherapy were randomized (1:1) to receive lamivudine 100 mg daily 1 week before chemotherapy (group 1) or to have this treatment deferred until there was serological evidence of hepatitis B virus reactivation on the basis of serial 2-week-interval serum hepatitis B virus DNA monitoring by a Digene Hybrid Capture II assay (group 2). RESULTS: Eight (53%) patients in group 2 and none in group 1 had hepatitis B virus virological reactivation after chemotherapy (P = 0.002). Seven patients in group 2 still had hepatitis (5 anicteric hepatitis, 1 icteric hepatitis, and 1 hepatic failure). Survival free from hepatitis due to hepatitis B virus reactivation in group 1 patients was significantly longer than that in group 2 (P = 0.002 on the log-rank test). The median onset of hepatitis B virus reactivation in these patients was 16 weeks (range, 4-36 weeks) after the initiation of chemotherapy. Three (13%) of the 23 patients treated with lamivudine had hepatitis B virus-related hepatitis after lamivudine withdrawal. CONCLUSIONS: Lamivudine should be considered preemptively before or at the initiation of chemotherapy for all hepatitis B surface antigen-positive lymphoma patients undergoing intense chemotherapy.